p38beta2-mediated phosphorylation and sumoylation of ATF7 are mutually exclusive.
The ubiquitous activating transcription factor (ATF) 7 binds as a homodimer to the cAMP response element/TPA response element motifs present in the promoters of its target genes. ATF7 is homologous to ATF2 and heterodimerizes with Jun or Fos proteins, modulating their DNA-binding specificities. We previously demonstrated that TAF12, a component of the TFIID general transcription factor, mediates ATF7 transcriptional activity through direct interactions between the two proteins. By contrast, ATF7, but not ATF2, is modified in vivo by sumoylation, which restricts its subcellular localization, thereby inhibiting its transcriptional activity. In the present study, we dissect the mechanism of this functional switch. We characterized the multisite phosphorylation of the ATF7 activation domain and identified one of the involved kinase, p38beta2 mitogen-activated protein kinase. In addition, we show that epidermal growth factor treatment results in a two-step modification mechanism of ATF7 activation domain. The Thr53 residue is phosphorylated first by a presently unknown kinase, allowing p38beta2 mitogen-activated protein kinase to modify the Thr51 residue, excluding the sumoylation of ATF7 protein. The resulting activation of transcription is related to an increased association of TAF12 with this phosphorylated form of ATF7. Our data therefore conclusively establish that sumoylation and phosphorylation of ATF7 are two antagonistic posttranslational modifications.
Camuzeaux
Barbara
B
Université de Strasbourg I, Institut Gilbert Laustriat, CNRS-UMR7175, Ecole Supérieure de Biotechnologie de Strasbourg, BP10413, Strasbourg Illkirch Cedex, France.
Diring
Jessica
J
Hamard
Pierre-Jacques
PJ
Oulad-Abdelghani
Mustapha
M
Donzeau
Mariel
M
Vigneron
Marc
M
Kedinger
Claude
C
Chatton
Bruno
B
D051696:Activating Transcription Factors / Q000378:metabolism*; D048290:Mitogen-Activated Protein Kinase 11 / Q000378:metabolism*; D010766:Phosphorylation; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D014158:Transcription, Genetic
C427752:ATF7 protein, human; D051696:Activating Transcription Factors; D025841:Small Ubiquitin-Related Modifier Proteins; D048290:Mitogen-Activated Protein Kinase 11